Triggering of the lethal hit in human cytotoxic T lymphocytes: a functional role for a 103‐kDa T cell‐ specific activation antigen

Fleischer, Bernhard; Schendel, Dolores J.; Steldern, D von

doi:10.1002/eji.1830160705

Cited by 34 publications

(15 citation statements)

References 23 publications

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“…The use of mAb CB. 1 allows CTL to be triggered independently from the antigen-receptodT3 complex [14].…”

Section: Discussionmentioning

confidence: 99%

“…The mAb CB.l against a 103-kDa T cell-specific triggering molecule (Tp103) was obtained from a fusion of P3-X63Ag8.653 myeloma cells with BALBic spleen cells immunized with a human CTL clone. As reported elsewhere [14] cross-linking of the 103-kDa T cell surface molecule and Fc receptors (FcR) on target cells via mAb CB.l triggers the lethal hit. Tp103 is only expressed on normal proliferating T cells and not on any of the target cells used.…”

Section: Monoclonal Antibodies (Mab)mentioning

confidence: 94%

“…Tp103 is only expressed on normal proliferating T cells and not on any of the target cells used. Tp103 is not associated with the T cell receptorE3 complex or the T11 antigen and induction of cytotoxicity is strictly dependent on the presence of FcR on target cells [14].…”

Section: Monoclonal Antibodies (Mab)mentioning

confidence: 99%

“…The possibility to trigger CTL via the 103-kDa T cell antigen detected by mAb CB.l [14] allowed us to investigate if triggering of CTL via an alternative, nonreceptor pathway would also lead to bystander lysis. Since triggering via CB.l is strictly dependent on the presence of FcR on the target cell, any FcRtarget cell could be used as bystander target.…”

Section: "Linked" and "Unlinked" Bystander Lysismentioning

confidence: 99%

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Lysis of bystander target cells after triggering of human cytotoxic T lymphocytes

Fleischer¹

1986

Eur J Immunol

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Human cloned cytotoxic T lymphocytes (CTL) specific for class I HLA antigens were used to investigate whether triggering of CTL leads to killing of innocent bystander target cells. After triggering of CTL by their specific target cells, lysis of bystander targets was detected in a 7-h cytotoxicity assay. Considerable differences were found in the susceptibility of various target cells to this type of lysis. Targets susceptible to this bystander lysis were also susceptible to lysis by CTL triggered by F(ab')2 fragments of an anti-T3 monoclonal antibody, whereas other targets were resistant to both types of cytotoxicity. Triggering of CTL by oxidized target cells or via a T3-independent activation pathway led to bystander lysis detectable already after 4 h. Bystander lysis was considerably enhanced under conditions that facilitated a non-specific cell contact between CTL and bystander target. We conclude that a function besides antigen recognition of the T cell receptor on CTL is to direct killing to the target cell. This directing, however, is incomplete and destruction of innocent bystanders can be detected under appropriate conditions.

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“…The use of mAb CB. 1 allows CTL to be triggered independently from the antigen-receptodT3 complex [14].…”

Section: Discussionmentioning

confidence: 99%

Section: Monoclonal Antibodies (Mab)mentioning

confidence: 94%

Section: Monoclonal Antibodies (Mab)mentioning

confidence: 99%

Section: "Linked" and "Unlinked" Bystander Lysismentioning

confidence: 99%

See 2 more Smart Citations

Lysis of bystander target cells after triggering of human cytotoxic T lymphocytes

Fleischer¹

1986

Eur J Immunol

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“…Some molecules, such as interleukin-2 receptors (IL-2R), transferrin receptors (TrR), insulin receptors, 4F2, and early activation antigen 1, appear early, even before DNA synthesis (1-5). Others, such as HLA-DR, CB.1, Ta,, T lineage-specific activation antigen 1 (TLiSA-l), and T10, appear more slowly (2-6 days) on activated T cells and seem to be expressed after DNA synthesis (2, [6][7][8].…”

Section: Very Late Activation Antigen On Synovial Fluid T Cells From mentioning

confidence: 99%

Very late activation antigen on synovial fluid T cells from patients with rheumatoid arthritis and other rheumatic diseases

Laffón

Sánchez-Madrid

Landázuri

et al. 1989

Arthritis & Rheumatism

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We used flow cytometry and immunoprecipitation techniques to study the expression of the activation molecules transferrin receptor, interleukin-2 receptor, HLA-DR, and very late activation antigen 1 (VLA-1) on purified T lymphocytes from peripheral blood and synovial fluid of 9 patients with rheumatoid arthritis and 7 patients with other rheumatic diseases. We found a T cell subset bearing VLA-1 in synovial fluid from 8 rheumatoid arthritis patients and 4 patients with other rheumatic diseases. VLA-1 was not found in peripheral blood T lymphocytes from either group.Antigen or mitogen stimulation of resting T lymphocytes results in T cell proliferation accompanied by the acquisition of various effector functions. In the course of T cell activation, a number of cell surface glycoproteins are newly expressed and follow a distinct kinetic pattern of appearance.

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The use of hybrid hybridomas to target human cytotoxic T lymphocytes

Lanzavecchia¹,

Scheidegger²

1987

Eur J Immunol

179

121

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This study describes a general strategy to produce hybrid monoclonal antibodies that are capable of targeting human cytotoxic T lymphocytes (CTL) against any cell carrying the appropriate target antigen. This is done by fusing a HAT-sensitive, G418-resistant anti-T3 hybridoma with immune spleen cells (or with other hybridomas) that produce antibodies against the desired target antigen. In the hybrid hybridomas the reassortment of Ig heavy and light chains results in the production of bifunctional antibody molecules. Because of their double specificity, these antibodies are able to bridge human CTL to target cells and trigger cytotoxic function. We have isolated several stable hybrid hybridomas in which one specificity is against T3 and one either against HLA antigens (class II, DC-1, A3), human Ig (IgM, IgE, kappa), Toxoplasma gondii or an ovary carcinoma-associated antigen. In all of these cases we show that culture supernatants can efficiently and specifically target any CTL clone against any target cell that possesses the relevant surface antigen recognized by the antibody. Furthermore, the killing requires as little as 0.1 ng/ml of antibody, occurs at effector to target ratios comparable to those used in conventional cytotoxic assays and does not affect bystander cells. Nonspecific killing of Fc receptor-positive cells can be avoided using F(ab')2 fragments. As an example, we show that it is possible to change the major histocompatibility complex class and allospecificity of a CTL clone and target CTL against non-major histocompatibility complex antigens such as Ig, parasites and tumor-associated antigens.

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Triggering of the lethal hit in human cytotoxic T lymphocytes: a functional role for a 103‐kDa T cell‐ specific activation antigen

Cited by 34 publications

References 23 publications

Lysis of bystander target cells after triggering of human cytotoxic T lymphocytes

Lysis of bystander target cells after triggering of human cytotoxic T lymphocytes

Very late activation antigen on synovial fluid T cells from patients with rheumatoid arthritis and other rheumatic diseases

The use of hybrid hybridomas to target human cytotoxic T lymphocytes

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